Extracellular potassium concentration; perhexiline and SKF-525A on the action of ouabain in isolated self-beating rat auricles.

The influences of different extracellular K+ concentrations and of blockers of potassium and calcium movements through cell membranes (perhexiline and SKF-525A) on the effects of ouabain on self beating isolated rat atria, both "non toxic" (positive inotropism without changes in contractile frequency or resting tension) and "toxic" (positive chronotropism, negative inotropism, contracture, arrhythmia), were explored. Decreasing extracellular K+ from 6 to 3 mM potentiated both the positive inotropic influences as well as the "toxic" effect of ouabain, whereas, increasing K+ from 6 to 8 mM delayed but potentiated the onset of the "non toxic" influences of the drug and abolished its "toxic" responses. Perhexiline and SKF-525A, sensitized the tissue to the "non toxic" effects of the glycoside, attenuated contracture but increased the positive chronotropic action. The aforementioned results suggest that factors which modify potassium environment (i.e., variable extracellular potassium concentration and ion-flux blocking agents) resulted in significant modification of the effect of ouabain on isolated rat myocardium.